What are the different therapies to treat Acne Vulgaris?

Acne Vulgaris Therapies and Treatments

Acne is a chronic skin disease characterized by open or closed comedones and inflammatory lesions, including papules, pustules, and nodules. Acne progresses through four stages, increased sebum production by sebaceous glands, follicular colonization, release of inflammatory mediators, and increased follicular keratinization. Circulating androgens cause sebaceous glands to increase their size and activity, there is increased keratinization of epidermal cells and development of an obstructed sebaceous follicle. Cells adhere to each other, forming a dense keratinous plug. Increased amounts of sebum production become trapped behind the keratin plug and solidifies, contributing to open or closed comodone formation. Noninflammatory acne lesions include closed and open comedones, also known as whiteheads and blackheads. Closed comedones are the first visible lesion in acne, they are almost completely obstructed to drainage and tend to rupture. Open comedones are formed as the plug extends to the upper canal and dilates its opening. Inflammatory acne lesions include papules, pustules, and nodules. Pus formation occurs due to recruitment of neutrophils into the follicle during the inflammatory process and release of Propionibacterium acnes generated chemokines.

               When treating acne vulgaris, the goals of treatment are to reduce the number and severity of lesions, improve appearance, slow progression, limit duration and recurrence, prevent disfigurement from scarring and hyperpigmentation, and avoid psychologic suffering. The most critical treatment target is the microcomedone. Eliminating follicular occlusion will arrest the whole acne cascade. Nondrug and pharmacologic treatment and preventive measures should be directed toward cleansing, reducing triggers, and combination therapy targeting all four pathogenic mechanisms. Combination therapy is often more effective than single therapy and may decrease side effects and minimize resistance or tolerance to individual treatments.  The approach to treatment depends on the severity index, types of lesions, treatment preferences, cost, skin type, age, adherence, response to previous therapy, presence of scarring, psychological effects, and family history of persistent acne. Topical therapy is the standard of care for mild-moderate care with systemic therapy used for moderate-severe acne.

There are multiple therapies available for the treatment of acne. This includes both nonpharmacologic and pharmacologic therapy. Nonpharmacologic therapies include physical treatments. This can be comedone extraction, cryotherapy, intralesional corticosteroids and optical treatments such as UV light. Pharmacologic therapy can be divided into topical and systemic therapy. Topical therapy ranges from retinoids and antibiotics to diverse treatments. Retinoids include adapalene, isotretinoin, tazarotene and tretinoin. Topical antibiotics include clindamycin and erythromycin. Other topicals include azelaic acid, benzoyl peroxide, chemical peels, corticosteroids, dapsone, hydrogen peroxide, niacinamide, salicylic acid, sodium sulfacetamide, and triclosan. Systemic therapies also include retinoids such as isotretinoin. Systemic antibiotics that are used are more wide range including azithromycin, clindamycin, doxycycline, erythromycin, levofloxacin, and minocycline. Hormonal contraceptives are also used in certain cases. Other treatments include corticosteroids, ibuprofen, or zinc sulfate. These are only a few of the many acne treatments that can be used. Monotherapy with any of these treatments or a combination of treatment can be used based on several factors from severity to type to patient preference.

References

Fox, L., Csongradi, C., Aucamp, M., du Plessis, J., & Gerber, M. (2016). Treatment Modalities for Acne. Molecules, 21(8), 1063. https://doi.org/10.3390/molecules21081063

Sibbald D (2020). Acne vulgaris. DiPiro J.T., & Yee G.C., & Posey L, & Haines S.T., & Nolin T.D., & Ellingrod V(Eds.), Pharmacotherapy: A Pathophysiologic Approach, 11e. McGraw Hill. https://accesspharmacy-mhmedical-com.jerome.stjohns.edu/content.aspx?bookid=2577&sectionid=231922868

Different Therapies for Acne Vulgaris

Acne vulgaris is a chronic and self-limiting inflammatory skin disorder of the pilosebaceous unit. According to the Global Burden of Disease Study of 2010, acne vulgaris is the 8th most common skin disease. Clinical manifestations include seborrhoea, comedones, erythematous papules and pustules, nodules, pustules or pseudocysts, and scarring. It commonly erupts on the face but can also appear on the upper arms, trunk, and back. There are four main pathogenetic mechanisms of acne: increased sebum production, follicular hyperkeratinization, Propionibacterium acne (P. acne) colonization, and the products of inflammation. Acne can be caused by medications (lithium, steroids, anticonvulsants), excessive sunlight exposure, occlusive clothing (headbands, underwire brasseries), endocrine disorders (i.e. PCOS), genetic factors, and puberty. Of the affected individuals, about 20% will develop severe acne that may lead to scarring. Severe acne frequents in Asians and Africans whereas mild acne commonly manifests Caucasians. Likewise, individuals with darker skin are more likely to develop hyperpigmentation. Depending on the severity, it can be treated over-the-counter, prescription only, or invasive procedures (incision and drainage). Typically, topical therapies are considered first line in mild to moderate acne whereas oral therapies are reserved for moderate and severe forms of acne.

Acne is common in adolescent populations, especially in males. Sebum secretion is increased during puberty where 5-alpha reductase converts testosterone to dihydrotestosterone (DHT), which binds to receptors in the sebaceous glands thereby increasing sebum production. Consequently, the follicular epidermis hyper-proliferates and retains sebum. The follicles swell and rupture, releasing pro-inflammatory chemicals into the dermis that lead to inflammation. Bacteria, C. acnes, Staphylococcus epidermidis, and Malassezia further prompt inflammation and follicular epidermal proliferation. Factors that aggravate acne include: food with a high glycemic number (i.e. dairy products and chocolate) which cause insulin-like growth factors that stimulate follicular epidermal hyperproliferation, oil-based cosmetics, and premenstrual flare-ups due to edema of the pilosebaceous duct. The mainstay of acne treatment include topical active ingredients containing benzoyl peroxide, antibiotics, or retinoids, and can be given in combination in refractory patients. Systemic modalities include oral antibiotics, hormonal therapy, and isotretinoin (in severe or refractory patients). Diagnosis of acne requires clinical evaluation.

Below are the different acne therapies: topical and systemic

Topical

-Topical benzoyl peroxide (available in combo with adapalene) 2.5%, 4%, or 5% concentration in gel base

*Counsel patient to avoid unnecessary sun exposure; apply sunscreen daily

-Retinoic acid 0.025%, 0.05%, or 0.1% cream or gel (comedolytic agent)

-Adapalene

-Tretinoin

-Topical clindamycin 1% - 2%

-Nadifloxacin or Azithromycin 1% gel or lotion

-Salicylic acid (beta hydroxy acid) topical gel 2% or chemical peel from 10%-20% for seborrhoea and comedonal acne

Systemic

Antibiotics

-Doxycycline 100 mg BID: it is an antibiotic and anti-inflammatory drug that affects free fatty acid secretion and helps control inflammation.

-Minocycline 50 mg and 100 mg capsules QD

*Other antibiotics that are occasionally used include amoxicillin, erythromycin, and trimethoprim/sulfamethoxazole

Retinoid

-Isotretinoin is potent and is often used for severe acne or refractory patients. It is teratogenic and those prescribed isotretinoin must follow through the REMS Program. It is dosed 0.5 mg/kg to 1 mg/kg body weight in daily or weekly pulse regimen. It controls sebum production, regulates pilosebaceous epidermal hyperproliferation, and reduces inflammation by controlling P. acnes.

*Common side effects include skin dryness and chelitis (cracked lips).

Oral Contraceptive

-For severe, recurrent acne, low dose estrogen 20 mcg along with cyproterone acetate as anti-androgens are used

Aldosterone Receptor Antagonist

-Spironolactone (25 mg per day) decreases the production of androgens and blocks the actions of testosterone.

Although acne is a self-limiting skin disorder, it is important for healthcare providers to recognize the complications that are associated in affected individuals, which include depression, anxiety, low-self esteem, and socially withdrawn behaviors, and optimize care accordingly. Nonpharmacologic recommendations include avoiding trigger foods (if applicable, i.e. spicy foods, dairy) and incorporating a high protein, low-glycemic diet.

References

Heng, Anna Hwee Sing, and Fook Tim Chew. “Systematic Review of the Epidemiology of Acne Vulgaris.” Nature News, 1 Apr. 2020, www.nature.com/articles/s41598-020-62715-3.

Sutaria, Amita H., et al. “National Center for Biotechnology Information.” Acne Vulgaris , 16 Feb. 2023, www.ncbi.nlm.nih.gov/books/NBK459173/.

Written by Aleksandra Agranovich

Acne Vulgaris

Acne Vulgaris is a very common skin condition that often affects young adults, adolescents, and teenagers. As a person grows older, the progression of this conditions tends to slow or cease all together. The pathophysiology of acne vulgaris can often be a result of bacterial infection, excessive sebum production, altered keratinization, and inflammation. Other factors that may also contribute to acne may include diet, the environment, and genetics.

The onset of acne vulgaris typically occurs during puberty or when the body begins to stimulate hormones like estrogen, progesterone, and testosterone. Although acne vulgaris can be treated, this condition may negatively impact a person’s quality of life, self-esteem, and possibly lead to facial scarring.

There are many different types of treatments available for acne vulgaris including topical therapies like benzoyl peroxide, retinoids, and antibiotics. Some guidelines even recommend combined oral contraceptives for women who have mild to moderate acne.

According to recommended guidelines, patients who experience more severe symptoms of acne vulgaris usually need combinations of oral antibiotic therapy with topical benzoyl peroxide to decrease antibiotic-resistant bacterial strands (Williams, 2012). In addition to antibiotics, retinoids (such as oral isotretinoin or tretinoin), may be the most effective therapy when used early on. Preventative measure for acne vulgaris includes smoking cessation, a balanced diet, and the removal of skin irritants.

Topical Steroids

Topical steroids may be used for a variety of skin conditions including dermatitis, acne vulgaris, eczema, urticaria, etc… Steroids such as clobetasol, triamcinolone, hydrocortisone, and betamethasone work by reducing inflammation, itchiness, and swelling. For certain conditions such as acne fulminans, topical steroids may be the best treatment option. Acne fulminans is a very serve and rare skin disorder that presents with hemorrhagic acne and painful lesions. Although hydrocortisone cream may be found over the counter in any local pharmacy, other types of topical steroids may only be dispensed by prescription. Long term use of topical steroids is not recommend because skin discoloration, redness, burning, and worsening of a condition.

Resources

Knutsen-Larson, Siri et al. “Acne vulgaris: pathogenesis, treatment, and needs assessment.” Dermatologic clinics vol. 30,1 (2012): 99-106, viii-ix.

doi:10.1016/j.det.2011.09.001

Krafchik, B R. “The use of topical steroids in children.” Seminars in dermatology vol. 14,1 (1995): 70-4. doi:10.1016/s1085-5629(05)80043-4

Williams, Hywel C et al. “Acne vulgaris.” Lancet (London, England) vol. 379,9813 (2012): 361-72. doi:10.1016/S0140-6736(11)60321-8

Acne Vulgaris Pathophysiology & Treatment

Acne vulgaris is a common skin condition which most commonly affects adolescents but may also affect adults. In patients with acne vulgaris, the pilosebaceous unit is affected by processes that lead to bacterial overgrowth and inflammation. The first process affecting the pilosebaceous follicle is follicular hyperkeratinization. In normal skin, keratinocytes are shed into the luman as single cells which are then excreted. In patients with acne, Hyperkeratinization occurs during periods of growth and increased cell turn over. This results in cohesion of multiple dead skin cells creating a plug at the epithelial layer known as a comedone. Comedones which are closed are identified as white heads while comedones which are open are known as black heads. The next process contributing to acne is increased sebum production. This is due to increases in androgenic hormones such as DHEA-S. This relates to the next process which is bacterial colonization with Propionibacterium acnes. The increased sebum provides an environment for the bacteria to thrive in as the bacteria uses triglycerides in sebum as a nutrient source. The last process is the recruitment of neutrophils due to bacterial growth which causes inflammation and redness on the skin surrounding an acne lesion.

Acne presents as comedones, papules, cysts nodules, or primarily inflammation depending on the stage of development. Treatment of acne is based on the severity. Mild acne is treated with either benzoyl peroxide, topical retinoid, or a combination of the two. Benzoyl peroxide releases free-radical oxygen which oxidizes bacterial proteins in the sebaceous follicles decreasing the number of bacteria. It also has mild anti-inflammatory and comedolytic properties. Topical retinoids work by stabilizing the follicular epithelium and preventing further shedding of the skin. Retinoids also work to clear preexisting microcomedones which is why patients who use these topical products experience a worsening of acne before any improvement is seen. If these two topical products do not produce an improvement for mild acne, topical clindamycin 1% or erythromycin 2% may be added to their regimen.

For the treatment of moderate acne, the concentration of topical retinoid or benzoyl peroxide may be increased. Addition of an oral antibiotic is also recommended. Doxycycline or minocycline are antibiotics of choice for acne. These work by inhibiting protein synthesis by binding to the 30S subunit of the bacterial ribosome.

Treatment of severe acne consists of a four-medication regimen: combination of a topical retinoid with benzoyl peroxide plus an oral and topical antibiotic if not already used or adding an adjunctive therapy such as isotretinoin or hormonal therapy. Oral isotretinoin works by reducing sebaceous gland size and reducing sebum production. Isotretinoin is highly effective but due to its potency it is reserved for refractory nodular and cystic acne or for patients with scarring. Hormonal therapy, in the form of oral contraceptives, can be used for females with severe acne. These work by reducing the sebum production that is initially increased by androgens. Progestins are preferred because they do not have any androgenic activity.

In addition to using pharmacologic treatment, patients with acne should wash their face twice daily with a mild astringent that is pH balanced, free of harsh chemicals and free of perfumes and dyes. They should use their hands or a soft washcloth in order to prevent further irritation.

Resources:

Fox L, Csongradi C, Aucamp M, du Plessis J, Gerber M. Treatment Modalities for Acne. Molecules. 2016;21(8):1063. Published 2016 Aug 13. doi:10.3390/molecules21081063

Lance R. Nelson, Acne Vulgaris, Reference Module in Biomedical Sciences, Elsevier, 2021,

ISBN 9780128012383, https://doi.org/10.1016/B978-0-12-818872-9.00015-7.

(https://www.sciencedirect.com/science/article/pii/B9780128188729000157)

Adapalene

Adapalene is a topical retinoid for the treatment of acne vulgaris. With acne, the skin cell turnover is in overdrive because old cells aren’t discarded when new cells are being produced. Then, the old cells, sebum and bacteria clogs the pore. Topical retinoids are used as first-line treatment because they modulate epidermal growth and differentiation, stimulate humoral and cellular immunity, decrease inflammatory response and reduce cell proliferation. There are other topical retinoids such as tretinoin and tazarotene, but their use is limited due to skin irritation and low tolerability. Adapalene, a third-generation synthetic retinoid, was then developed to improve the side effect profile. Compared to other retinoids, adapalene is shown to be gentler, but just as effective.

In 1996, adapalene was FDA approved as a prescription retinoid acne treatment in patients 12 years of age or older. Then, in 2016, adapalene 0.1% received FDA approval for use without a prescription in patients 12 years of age or older. As a result, adapalene 0.1% is the only topical retinoid available over the counter. Other products containing adapalene are still available with a prescription.

Adapalene prevents and treats acne by regulating skin cell turnover to keep pores from clogging and reducing redness and underlying inflammation. It also helps in restoring the natural texture and tone of the skin. Some side effects of adapalene include photosensitivity, irritation, redness, dryness, itching and burning. Adapalene is contraindicated in pregnancy, photosensitive disorder, eczema, sunburn or concomitant use of other potentially irritating skincare products.

Differin Gel is a popular skin product containing the active ingredient adapalene. In a clinical study, it is shown that after 12 weeks of using Differin Gel, there is an 87% decrease in acne. It starts working immediately, and results may be seen in as little as two weeks. It may take time to see significant change, but it has been proven to work with continued use. Using Differin Gel may result in retinization which is an adjustment period when the skin adapts to the retinoid. Skin irritation may occur in the first few weeks of use and/or if using more than one topical acne product at the same time. Therefore, it is advised to avoid salicylic acid, alpha hydroxy acid, or glycolic acid when using adapalene because it may dry out the skin and worsen the irritation. Irritation should subside after about 4 weeks of use, and it is a common reaction that should not discourage use. However, prolonged symptoms of severe irritation is a sign to stop use and consult the physician.

Differin Gel is applied once daily to a clean, dry face. Only a pea sized amount should be applied as a thin layer to the entire face. Applying more than directed will not provide faster or better results. Differin Gel is also not a spot treatment and should not be used to treat a single pimple. Then, moisturizer should be applied on top to decrease irritation. And if used in the morning, it is important to apply sunscreen on top to avoid photosensitivity.

References:

1. “Differin Gel: An over-the-Counter Retinoid for Acne.” Frequently Asked Questions | Differin Gel, https://differin.com/learn/faqs.

2. Galderma. “Differin Gel: An over-the-Counter Retinoid for Acne.” What Is Adapalene Topical Retinoid for Acne? | Differin Gel, https://differin.com/learn/adapalene.

3. Piskin S, Uzunali E. A review of the use of adapalene for the treatment of acne vulgaris. Ther Clin Risk Manag. 2007;3(4):621-624.

4. Tolaymat L, Dearborn H, Zito PM. Adapalene. In: StatPearls. Treasure Island (FL): StatPearls Publishing; January 4, 2022.

The Innovation of Retinoids: Trifarotene

Acne vulgaris is a common skin disorder encompassing increased sebum production, inflammation and follicular hyperkeratinization. There is a myriad of treatments, but retinoids have been the cornerstone of acne treatment for some time now. This is because our skin is comprised of retinoic acid receptors (RARs) α, β, and γ and retinoid X receptors (RXRs) α, β, and γ. Once bound by retinoids, these nuclear transcription factors are activated and generate anti-proliferative and anti-inflammatory effects. One of the most commonly prescribed retinoids by dermatologists is tretinoin. First approved by the FDA in 1971, tretinoin is a nonselective retinoid with an equal affinity to all RAR subtypes. Since then, researchers have overcome the drawbacks of tretinoin and created more target-specific therapies such as adapalene and tazarotene, ultimately bringing us to where are today with trifarotene, an innovative fourth generation retinoid. It was approved for the treatment of facial and truncal acne in patients aged 9 years or older, in October 2019. What makes Trifarotene an optimal choice is it has a 20x greater affinity for the RAR-γ receptors than RAR-α and RAR-β receptors and no affinity towards RXR receptors. This is extremely important as RAR-γ is most dominant subtype of retinoic acid receptor in the skin. Trifarotene’s potent selectivity allows it to be highly efficacious as compared tretinoin, who binds to all three receptors and third-generation retinoids (Adapalene and Tazarotene) who bind to RAR-β and RAR-γ receptors. During its two-phase III double-blind, randomized, vehicle-controlled trials of 12-week duration study, acne symptoms improved substantially with trifarotene 0.005% cream than with the vehicle cream. Investigator’s Global Assessment (IGA) success rates were higher in the trifarotene than vehicle group (29.4 vs 19.5% in PERFECT 1; 42.3 vs 25.7% in PERFECT 2). Improvement of acne symptoms continued beyond the initial 12 weeks over the 52-week study period. In the U.S., there is one formulation available, Aklief 0.005% Cream (45 g) patented by Galderma Laboratories. It is recommended applying a thin layer to the affected areas once daily, in the evening, on clean dry skin. Studies showed systemic concentrations reached steady state after 2 weeks of treatment with once-daily topical trifarotene. Adverse effects include application site irritation, sunburn and itchiness. Because of trifarotene’s efficacy and potency, I hope it gains popularity as the go-to retinoid for the treatment of acne vulgaris.

Reference:

• Kassir, Martin. “Selective RAR Agonists for Acne Vulgaris: A Narrative Review.” Wiley Online Journal, Feb. 2020.

• Scott, Lesley. “Trifarotene: First Approval.” Springer Link, Nov. 2019.

• “Your Go-to for Acne Relief.” Why AKLIEF? | Patient | AKLIEF® (Trifarotene) Cream, 0.005%.

Donna Salib & Natalie Eshaghian

Acne Vulgaris and the Use of Chemical Peels

Acne Vulgaris is a skin disease that creates a red ring on the skin with a white head in the center. This is formed when there is an active blockage of the skin pore, and this blockage can be an accumulation of sebum (a natural oil), dead skin cells, and more (1) Due to oil being a significant blockage, teenagers are most vulnerable to acne due to their hormonal changes resulting in the stimulation of their oily glands. Often people attempt to treat their acne by puncturing the white head in their pimple and waiting for it to heal. This can cause scarring and acne can be recurring which makes this treatment ineffective. Another method that people turn to is chemical peels. A chemical peel is a treatment in which a chemical solution is placed upon the skin of a patient in hopes of burning a layer of the skin so that new healthy skin grows back. The basis of peels originates from the Egyptian era when Queen Cleopatra used a milk bath as part of her beauty regime. This milk bath consisted of lactic acid which is one of the first known peels that's known for hydration of the skin as well as exfoliation. The purpose of chemical peels is to expose fresher skin and shed dead skin.

Chemical peels also cause collagen stimulation and improve skin texture. They are used for oily or acne-prone skin, fine lines, or photo-damaged skin which includes brown spots on the skin. There are different types of chemical peels and the ones used are dependent upon what the patient wishes. The most common chemical peel is one called a superficial peel, which peels the upper part of the skin, known as the stratum corneum, and the epidermis but not past the basement membranes. If the patient wants only a gentle exfoliation they would get a superficial peel that uses only mild acids. If they want something more serious but do not want to damage the skin too much there are medium peels that use slightly more harsh chemicals and reach the middle and outer layer of the skin. Finally, there are deep peels that use the most severe available chemicals (phenol or trichloroacetic acid) which completely breaches the middle layer of the skin to remove the accessible dead skin cells (2)

In reference to acne, chemical peels can be successful in terms of removing skin disease and acne scarring from a patient’s skin. Initially following the treatment chemical peels can cause general irritation of the skin, flakey or peeling skin, discoloration, and oftentimes more acne (due to the great number of dead skin cells this could cause more blockage. (3) However these symptoms are temporary and the process for healthy skin following a chemical peel is a lengthy one. According to the American Academy of Dermatology Association, to fully recover from a chemical peel, it takes about seven to fourteen days to heal from the treated areas and redness can last for months(4). Although chemical peels can be seen as a viable treatment for acne it does also offer a great number of limitations and significant drawbacks. Patients of chemical treatments must be responsible for the maintenance of their skin because following the treatment they are very vulnerable to serious skin problems, most notably skin infections. Due to the lack of protection from the destruction of a layer of skin, microbes such as bacteria and viruses are very capable of infecting a patient. Accordingly, those who undergo chemical treatments are instructed to take antiviral medication. Hyper-pigmentation is also a possible consequence which is a skin condition in which portions of skin appear darker than the majority areas of the skin. This occurs when an abundant amount of melanin deposits in the skin as the layers of skin grow back. To prevent this condition, patients are instructed to apply topical bleaching agents (hydroquinone) to create an even skin tone. Not only do deep peels contain between fifteen and fifty percent of a carcinogenic chemical named trichloroacetic acid but following the treatment, the skin is very vulnerable to skin cancer. However, currently, no information on systemic toxicity following dermal exposure of humans to chemical peels has been identified. (5)

As indicated prior, due to the destruction of a layer of skin there is significantly less protection for the skin, which leaves the skin unguarded to the harmful effects of direct sun exposure. UV rays from the sun can ultimately damage DNA and cause cancer therefore patients are told to apply sunscreens consistently and to make a conscious effort to avoid the sun until fully recovered from the chemical peel (6). Finally, the effects of a chemical peel are not permanent, so patients may need to get another one in the future and have to deliberate taking the same risks again. Overall, as acne vulgaris can be a very severe condition for some, chemical peels can be seen as a viable treatment. With the values of the chemical peel also come fearful limitations which may result in skin conditions worse than acne and it is very important for those considering this option to be fully educated on the treatment and all available options for them.

References:

1. Chen Y, Lyga J. Brain-skin connection: stress, inflammation and skin aging. Inflamm Allergy Drug Targets. 2014;13(3):177-190. doi:10.2174/1871528113666140522104422

2. Glogau RG, Matarasso SL. Chemical peels. Trichloroacetic acid and phenol. Dermatol Clin. 1995;13(2):263-276.

3. 10 things to expect after your first Chemical Peel. U.S. Dermatology Partners. Available at:https://www.usdermatologypartners.com/blog/what-to-expect-after-a-chemical-peel/#:~:text=Unfortunately%2C%20the%20combination%20of%20larger,few%20days%20and%20look%20healthier Published June 22, 2021.

4. Chemical peels: FAQs. American Academy of Dermatology. Available at: https://www.aad.org/public/cosmetic/younger-looking/chemical-peels-faqs Date Accessed: August 15, 2021

5. Sidiropoulou P, Gregoriou S, Rigopoulos D, Kontochristopoulos G. Chemical Peels in Skin Cancer: A Review. J Clin Aesthet Dermatol. 2020;13(2):53-57.

6. Khunger N; IADVL Task Force. Standard guidelines of care for chemical peels. Indian J Dermatol Venereol Leprol. 2008;74 Suppl:S5-S12.

Acne affects an estimated number of 50 million Americans annually. There are numerous different treatments for acne vulgaris. Acne lesions have different classifications which include black heads, white heads, small bumps, nodules, and cysts. It is natural for most patients to opt for over-the-counter products initially to see if anything works- as far as I’m concerned no one wants to go to the doctor unless he or she has to. Whether products are OTC or prescription, there are three shared main goals which are 1. To treat current acne, 2, To prevent new scars from forming, and 3. To treat current acne scars. Common active ingredients in over-the-counter acne products include benzoyl peroxide, salicylic acid, alpha hydroxy acids, and sulfur. The most common oral medications for acne include antibiotics, combined oral contraceptives, anti-androgen agents such as Aldactone (spironolactone), and isotretinoin. The most common topical prescription medications for acne include retinoids and retinoid-like drugs, antibiotics, azelaic and salicylic acid, and dapsone.

The Food and Drug Administration (FDA) has recently approved the first acne treatment with a new mechanism of action in 40 years- Winlevi (clascoterone cream 1%). As mentioned prior, acne is most commonly treated with a type of drug called retinoids in addition to antibiotics. During critical clinical trials it is important to note that Winlevi was shown to inhibit lipid production from oil producing cells (sebocytes) and reduce proinflammatory cytokines, mediators influenced by androgens. Winlevi 1% cream was well tolerated when used twice a day.

Dosage and Administration- First and foremost, the patient must cleanse the affected area gently. When the skin is dry, a patient should apply a thin layer of Winlevi cream twice per day- once in the morning and once in the evening to the affected area. Avoid contact of Winlevi with any mucous membrane including the eye and the mouth.

Mechanism of Action- Clascoterone is a first-in-class topical androgen receptor inhibitor that works on the androgen hormone component in both males and females. Androgen receptor inhibitors work by limiting the effects of these hormones in acne in the increase of the production and inflammation of sebum.

Adverse Reactions- The most common adverse effects and reactions to Winlevi are reddening of the skin, itchiness, and scaling/dryness. This occurs in roughly 7 to 12% of patients so it is important to be cognizant of it.

Warnings and Precautions- Warnings and precautions include local irritation such as burning, peeling, and skin redness. It is important to note that albeit Winlevi is solely approved for patients of the age 12 and older, pediatric patients may be more susceptible to systemic toxicity. As this is a cream, it’s important to consider certain factors such as ensuring that the cream is physically out of reach for pediatric patients. During or after treatment with Winlevi, hypothalamic-pituitary-adrenal (HPA) axis suppression may occur. Under medical supervision, a patient should attempt to withdraw use of Winlevi if HPA axis suppression occurs. Elevated potassium levels were also observed in some subjects during clinical trials so patients on Winlevi should also be cognizant of possible hyperkalemia.

References-

Acne- Treatment. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/acne/diagnosis-treatment/drc-20368048

Winlevi- Package Insert. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213433s000lbl.pdf

FDA Approves First Acne Treatment with New Mechanism of Action in 40 Years. Biospace. https://www.biospace.com/article/fda-approves-first-acne-treatment-with-new-mechanism-of-action-in-40-years/

When treating acne vulgaris in adults, general treatment modalities range from topical products to oral or procedural therapies depending on severity. The go to treatment is usually a topical agent but if a patient has a more severe presentation of acne they may benefit greatly from systemic therapies. There are four main factors in acne vulgaris pathogenesis, that include sebum production, follicular hyperkeratinization, inflammation, and C. acnes.

Oral isotretinoin is a well-known option for more severe, usually nodular acne. Common brand names include Absorica, Accutane, Myorisan, and Claravis. It is the only medication that targets all four factors of acne pathogenesis mentioned. It is also the only medication that can permanently alter the natural course of acne vulgaris and has the potential to induce long-term remissions off therapy. Isotretinoin would be the agent of choice if a patient’s clinical presentation was severe, or, if they failed other topical or systemic therapies like antibiotics. It’s a retinoid or retinoic acid derivative that is typically prescribed for a course of several months as monotherapy. Its mechanism of action is described as reducing sebaceous gland size and reducing sebum production in acne treatment. The common dosing regimen is 0.5 mg/kg/day in 2 divided doses for 1 month, then increasing to 1 mg/kg/day in 2 divided doses as tolerated. The patient should take this with food and a full glass of water.

This medication holds the risk of a severe acne flare when first starting it, so an oral glucocorticoid is commonly prescribed for the first few weeks a patient begins isotretinoin. As a pharmacist, we are responsible for counseling patients that their acne will probably get worse before improvement starts to show. It’s extremely important for the patient to keep taking it and be patient with their skin. We are also responsible for the iPledge risk evaluation program, which must be signed off and completed by both patient and doctor. This program exists because isotretinoin is highly teratogenic, so a female patient must display two negative pregnancy tests before beginning the medication and a monthly test thereafter. Patients should also use two forms of birth control for the months they are taking Isotretinoin. Pharmacists cannot dispense isotretinoin without this program being completed.

Other warnings or precautions include hepatic effects, auditory effects, hematologic effects, dermatological effects, ocular effects, psychiatric effects and many more. This is a high risk medication. More common side effects include dry mouth, lips and skin, vision changes and nose irritation.

1. ISOtretinoin (Systemic) (Lexi-Drugs). Hudson, Ohio. Lexicomp, Inc. Feb 2021.

2. Graber, Emma. Acne vulgaris: Management of moderate to severe acne. UpToDate. Jan 2021.

Acne vulgaris is one of the most common skin conditions that patients, especially adolescents, present with to primary care providers for consultation and recommendation. Acne can have negative effects on a person’s self-esteem which may lead to depression, anxiety, and suicidal thoughts. Acne vulgaris can be non-inflammatory (i.e. comedones) or inflammatory (i.e. papules, pustules, nodules or cysts). There are various reasons that can contribute to acne: keratinization of the follicles, sebum production, bacterial infection, genetics, or the release of inflammatory mediators. Bacteria such as P. acnes can cause keratinocytes to fissure and create comedones. While genetics can induce lipid synthesis of sebaceous glands. Other factors can be menstruation, occupation, sweat, diet, or stress. Treatments can vary from systemic, topical, or physical therapies. Some of the therapies that are not as widespread as others may be acupuncture, blue-light therapy, or chemical peels.

Blue-Light Therapy

407 – 420 nm wavelength of light is said to have bactericidal effect on P. acnes. It works by creating an excitatory effect where it leads to the release of oxygen and free radicals to create the bactericidal effects. There are various types of light for the treatment of acne (blue, red, and blue/red light). The use of blue-light therapy requires frequent use from patients who would want to see desired effects. Typical devices that patients can use at home will need to be used twice daily for 30-60 minutes for up to 4-5 weeks which may prove to be difficult for some patients with adherence issues. However, there is not much consistent evidence on the effectiveness of blue-light therapy for the treatment of acne. Some patients experience improvement which may vary by the duration and the size of the lesion, while some patients do not experience the same level or lack of improvement. Therefore, blue-light therapy is secondary treatment compared to topical treatments. It can be considered as an alternative to oral antibiotics for patients with severe acne vulgaris. Patients on blue-light therapy need to be monitored due to potential adverse effects such as skin irritation, dryness, and erythema.

Chemical Peels

Chemical peeling is a specific type of procedure that allows the skin to be regenerated and rejuvenated by mildly damaging it to make way for a new layer of the epidermis. There are different types of chemical peels: mild peels can cause superficial damage to the epidermis, moderate peels cause disruption to the papillary dermis and upper reticular dermis, or deep peels can cause destruction of the mid-reticular dermis and are used to treat deep acne scars. The chemical peels used for acne vulgaris is usually the mild superficial peels. Chemical peels can reduce the sebum production, kill bacteria, and affect the inflammation process which gives them the potential to be used as add-on therapy or maintenance therapy for acne. Studies have shown that chemical peels are relatively effective for treating acne. Combination peels with salicylic acid and mandelic acid are considered more effective than the use of glycolic acid alone. Chemical peels are also well-tolerated by patients with only mild adverse effects such as stinging, burning sensation, or dryness. Although the evidence from clinical trials appears promising, providers should still be careful when choosing the appropriate treatment for acne. This is because certain chemical peels, concentrations, and durations can negatively affect different types of skin. Overall, patients who present with mild to moderate acne vulgaris can use chemical peel treatment, however, they should be used with caution like other acne treatments.

Acupuncture

Acupuncture is a technique that is used to stimulate certain points in the body. There are different types of acupuncture, but the one that has seen positive results was auricular acupressure and surrounding needle. This is where 2-4 needles are placed into the epidermis around the lesion. Evidence has shown that this style of acupuncture can decrease the serum excretion rate and testosterone levels. Combination of acupuncture with benzoyl peroxide has shown significant reduction in the serum excretion rate compared to the use of benzoyl peroxide alone. In fact, studies have demonstrated that acupressure provides the same improvement of symptoms of acne as other pharmaceutical products with less adverse effects. Furthermore, acupuncture was seen to be just as effective as topical and oral retinoids. Treatment with acupuncture should still be treated with caution due to inconsistent reports.

References

Scott, A. M., Stehlik, P., Clark, J., Zhang, D., Yang, Z., Hoffmann, T., Mar, C. D., & Glasziou, P. (2019). Blue-Light Therapy for Acne Vulgaris: A Systematic Review and Meta-Analysis. Annals of family medicine, 17(6), 545–553. https://doi.org/10.1370/afm.2445

Chen, X., Wang, S., Yang, M., & Li, L. (2018). Chemical peels for acne vulgaris: a systematic review of randomised controlled trials. BMJ open, 8(4), e019607. https://doi.org/10.1136/bmjopen-2017-019607

Mansu, S., Liang, H., Parker, S., Coyle, M. E., Wang, K., Zhang, A. L., Guo, X., Lu, C., & Xue, C. (2018). Acupuncture for Acne Vulgaris: A Systematic Review and Meta-Analysis. Evidence-based complementary and alternative medicine : eCAM, 2018, 4806734. https://doi.org/10.1155/2018/4806734

Acne vulgaris, more readily known by the general population as common acne, is a chronic skin condition that involves the blockage of hair follicles and skin pores with dead skin cells, bacteria, and oil or sebum. Through this blockage, blackheads may form upon the skin surface. These blackheads may further develop into blemishes and whiteheads. In addition to blackheads and whiteheads, pimples may also form upon the skin due to inflammation and blocking of pores & follicles. Pimples clog excess sebum within the inflamed pore, leading to pus-formation. All pimples, whiteheads, and blackheads are classified as comedos.

Acne vulgaris is an incredibly common occurrence, affecting over 85% of teenagers and 50 million Americans every year. This condition is often a byproduct of hormone imbalances and changes, increased sebum production (oftentimes due to puberty or bodily changes), and drastic changes that may induce increased stress. While teenagers are most affected by acne vulgaris, this condition can and often does persist for some adults into their older years. Acne vulgaris is often classified by the severity of the disease, ranging form mild to moderate to severe. Mild acne vulgaris is classified by open comedones (blackheads) and white comedones (whiteheads) with few inflammatory papules or pustules (pimples.) On the other end of the spectrum, severe acne vulgaris consists of numerous papules and pustules that are painful in nature.

Treatment for acne vulgaris is most commonly achieved by first classifying the severity of one’s condition as first-line treatment and additional therapy may vary depending on the patient’s stratification. In the case of mild acne vulgaris where comedones are more present than pimples, a topical retinoid may be considered first-line therapy. Examples of topical retinoids include tretinoin, isotretinoin, adapalene, and alitretinoin. These compounds result in proliferation and reduced keratinisation of skin cells independent of their functions as a vitamin.If these first-line therapy options provide no benefit, then a salicylate or salicylic acid may be used as a suitable alternative.

As acne vulgaris progresses from comedone-predominant to papular and pustular, a topical antimicrobial agent may be added to a topical retinoid to provide an antibacterial effect. Some antimicrobials used topically in the treatment of acne vulgaris include benzoyl peroxide, clindamycin, and erythromycin. Once the acne has become moderate in severity, an oral antimicrobial (such as a tetracycline, trimethoprim+sulfamethoxazole, or erythromycin) may be initiated along with benzoyl peroxide and a topical retinoid. When acne vulgaris is classified as severe, oral or systemic isotretinoin may be initiated. The use of oral isotretinoin is heavily monitored through the iSTOP program due to the fact that isotretinoin is known for causing severe birth defects in those who are able to get pregnant.

References:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080563/

https://www.ncbi.nlm.nih.gov/books/NBK459173/

Spironolactone

This choice of therapy has been used in the dermatological setting even though its primary use is for cardiovascular properties. Although it is not generally considered a primary agent in the management of female patients with acne vulgaris, its mechanism of action placed a spotlight on the use of this agent in patients with hormonal acne vulgaris.

Mechanism of Action:

Spironolactone at doses of 50 to 200 mg/day reduces acne because it is an androgen receptor antagonist and inhibits 5-α-reductase. It has been shown to inhibit sebaceous gland activity. Clinically, women with high androgenic states will have increased sebum production due to an increase in circulating androgens.

Role of therapy:

It is an off-label use for women with hormonal-pattern AV, defined clinically as "primarily inflammatory papules, many deep-seated and tender, that are located predominantly on the lower half of the face and anterior-lateral neck region".

Potential Indications of Spironolactone Use

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315877/

Koda-Kimble, M. A., & Young, L. Y. (2001). Applied therapeutics: The clinical use of drugs. Baltimore, Md: Lippincott Williams & Wilkins.

Tazarotene

Tazarotene also known as Arazlo or Tazorac is a once daily topical retinoid that is approved by the FDA for use in treating acne vulgaris and plaque psoriasis. It’s exact mechanism of action is not well understood but it has shown to be a modulator of cell differentiation and proliferation in epithelial tissue. There have been a number of trials that have been conducted to assess the efficacy and safety of tazarotene in the treatment of both psoriasis and acne vulgaris. Two RCT with a total of 847 patients with acne vulgaris were treated with tazarotene 0.1% cream and placebo. After 12 weeks, there was a significantly greater reduction of lesions in the patients receiving the tazarotene (43% vs. 23 percent with placebo). In two trials that included a population size of 1303 people with psoriasis. Patients received either tazarotene creams 0.1% and 0.05% or placebo once daily for 12 weeks. The results showed that both concentrations were significantly effective in reducing psoriasis symptoms compared to placebo with the 0.1% tazarotene formulation causing more skin irritation. Another trial was conducted that compared tazarotene with a favorable topical corticosteroid and the results showed that tazarotene was just as effective and had less systemic absorption. Tazarotene use is limited due to skin irritation and this is why it is commonly administered with a corticosteroid. Tazarotene is available as a gel, foam, cream and lotion with concentrations of either 0.1% or 0.05%.

https://www.ncbi.nlm.nih.gov/pubmed?term=15639698

https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020600s009lbl.pdf

https://www.ncbi.nlm.nih.gov/pubmed?term=9591815

https://www.uptodate.com/contents/treatment-of-acne-vulgaris?search=Tazarotene&source=search_result&selectedTitle=2~35&usage_type=default&display_rank=1

https://www.uptodate.com/contents/treatment-of-psoriasis-in-adults?search=Tazarotene%20psoriasus&source=search_result&selectedTitle=5~37&usage_type=default&display_rank=5&id=treatment-of-psoriasis-in-adults&languageCode=en#H21

http://online.lexi.com.jerome.stjohns.edu:81/lco/action/doc/retrieve/docid/patch_f/7726?cesid=3RurMjDsLUP&searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3DTazarotene%26t%3Dname%26va%3DTazarotene#foc

As for oral antibiotics, it is usually reserved for patients who hasn't had satisfying results from topical therapies and for situations where lesions are widespread or in difficult-to-reach areas. It is important to note that oral antibiotics should be not be used as monotherapy, in fact, it is recommended to be paired with topical retinoids and potentially also benzoyl peroxide in patients with moderate to severe acne.

Frequent oral antibiotics used for acne are

1. Doxycycline: most convenient and effective

2. Tetracycline: Side effects of this category of antibiotics include "autoimmune disorders (such as lupus-like syndrome), intracranial hypertension, pseudotumor cerebri, eosinophilic pneumonitis, and hepatotoxicity".

3. Minocycline: significantly more expensive and not clearly better in efficacy, even in resistant acne. This medication comes with more side effects than other tetracycline antibiotics. Contraindications: pregnant women and children under the age of 9.

4. Erythromycin: associated with higher rates of resistance

5. Trimethoprim/ sulfamethoxazole

Alldredge, Brian K, Mary A. Koda-Kimble, and Lloyd Y. Young. Applied Therapeutics: The Clinical Use of Drugs. , 2013.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050614/

Just to add onto what was said, another treatment available are topical antibiotics. The most common antibiotics used include erythromycin and clindamycin. Bacteria on the skin naturally secrete substances that help it break down sebum, which it then consumes as food. As the number of bacteria increases, that secretion irritates surrounding tissue, resulting in an immune system response in the form of inflammation. Erythromycin is available in both gel and solution formulations, while clindamycin is available as a gel, solution, lotion and foam. These antibiotics are effective because they target the bacteria on this skin that infect your pores and cause acne. Clindamycin is a lincosamide antibiotic that reversibly binds to 50S ribosomal subunits of bacteria. This prevents peptide bond formation and inhibits bacterial protein synthesis. Erythromycin is a macrolide antibiotic that inhibits the RNA-dependent protein synthesis in the bacteria that causes the acne. Specifically they bind to the 50S ribosomal subunit and block the transpeptidation process. These antibiotics should not be used alone for the treatment of acne. The highest efficacy of these antibiotics was shown to be when these were combined with either benzoyl peroxide or retinoids. Benzoyl peroxide can decrease the bacterial resistance to the antibiotics. Erythromycin is usually comes in a 2% strength, while clindamycin usually comes in a 1% concentration.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678709/

https://www.ncbi.nlm.nih.gov/books/NBK83685/

Oral isotretinoin is the drug of choice for severe, nodulocystic acne and it is an isomer of retinoic acid.

Mechanism of action: Isotretinoin is the only therapy that impacts on "all of the major aetiological factors implicated in acne. It achieves this remarkable efficacy by influencing cell-cycle progression, cellular differentiation, cell survival, and apoptosis"

Counseling:

• There are different formulations of isotretinoin. One particular is Absorica and it can be taken with or without food, whereas generic products AB-rated to Accutane brand should be taken with food.

• Acne may worsen during the first month of therapy before it gets better

• It is teratogenic so it is contraindicated in pregnancy.

iPLEDGE program

A program that mandates registration of prescribers, patients, and pharmacies to prevent fetal exposure to isotretinoin. The iPLEDGE program requires that all patients meet qualification criteria and monthly program requirements. Before the patient receives his or her isotretinoin prescription each month, the prescriber must counsel the patient about the risks of isotretinoin and document it in the iPLEDGE system.

Female patients should be tested for pregnancy before initiation of therapy and instructed to use two methods of contraception beginning at least 1 month before initiation of therapy and continuing for 1 month after discontinuation of therapy.

Relapse Concerns:

Review articles regarding the use of this drug praise that not only does it clear acne in almost all patients, but long-term remission can also be achieved in 70-80% of patients with a single course.

Further Investigations:

New indications continue to emerge, particularly as a potential treatment for both intrinsic and extrinsic aging.

Layton A. (2009). The use of isotretinoin in acne.Dermato-endocrinology,1(3), 162–169. https://doi.org/10.4161/derm.1.3.9364

https://www.ncbi.nlm.nih.gov/pubmed/23013115

Topical Antibacterial Agents: Benzoyl peroxide

For Acne Vulgaris, topical therapy is the standard treatment for mild-to-moderate acne, whereas systemic therapy is required for moderate-to-severe acne. Benzoyl peroxide is bactericidal and also suppresses sebum production and reduces free fatty acids, which are comedogenic and inflammatory triggers. It is useful for both noninflammatory and inflammatory acne. It has a rapid onset and may decrease the number of inflamed lesions within 5 days. Used alone or in combination, benzoyl peroxide is the standard of care for mild to moderate papulopustular acne. benzoyl peroxide is equally effective at concentrations of 2.5, 5.0, and 10%. Randomized trials have shown that in concentrations of 2-4 %, their effects are comparable to oral tetracycline and minocycline. However, a concentration-dependent irritant dermatitis can occur with higher concentrations. The efficacy of benzoyl peroxide can be enhanced when used in combination with topical retinoids, antibiotics. Combination therapy with retinoids or benzoyl peroxide increases efficacy. Retinoids increase penetration and reduce comedones, while topical antibiotics primarily address inflammation.

Dose: Therapy should be initiated with the weakest concentration (2.5%). Once tolerance is achieved, the strength may be increased to 5%.

Counseling Point for patients: It is important to wash the product off in the morning. Sunscreen should be applied during the day.

Side effects: dryness, irritation, and, rarely, allergic contact dermatitis. It may bleach hair and clothing.

ncbi.nlm.nih.gov/pubmed/19761357

https://www.ncbi.nlm.nih.gov/pubmed/16638058